In human beings, development of chloracne is the most sensitive indicator of exposure to toxic polyhalogenated aromatic hydrocarbons. The mechanisms of pathogenesis of this disease are not known. It appears that epithelial cells lining the ducts of human sebaceous follicles are primary target organs and are transformed to an abnormal pattern of differentiation upon exposure to such chemicals. This results in formation of retention hyperkeratosis, comedones, and chloracne. To understand the mechanisms involved in this transformation, we propose to use experimental animals for in vivo, and human skin biopsies for in vitro studies to investigate the biochemical and metabolic parameters which may be affected upon exposure to dioxin and to polychlorinated biphenyls. Specifically, we will monitor certain enzymatic markers during experimentally induced chloracne in hairless mice and in rabbit ears. We will also examine the effect of dioxin and polychlorinated biphenyl exposure on sebaceous follicle lipid biosynthesis and androgen metabolism in in vitro assays, and on cellular kinetics of follicular epithelial cells in tissue culture. Finally we will attempt to identify the localization of aromatic hydrocarbons in skin, by using radiolabeled tracers. Because of the apparent selective sensitivity of follicular epithelial cells to polyhalogenated aromatic hydrocarbons, elucidating the mechanisms of toxicity for such cells may provide a better understanding of their mechanisms of toxicity in general.